Changes in cognitive function among older adults: A latent profile transition analysis

Cognitive decline in late life is a crucial health problem. It is important to understand the consistency and change of older adults’ cognitive function in late life. Data for older adults (78 years and above) from the Health and Retirement Study (N = 1680) were used to explore meaningful subtypes of cognitive function and transitions patterns between those profiles across times. Age, gender, levels of education and nursing home were incorporated as covariates to explore the association between these variables and cognitive function transition pattern. Three cognitive function subgroups (Normal Cognitive Function, Fluid Intelligence Impairment and Cognitive Impairment) were identified. Individuals in Normal Cognitive Function status had a high probability to convert to the Fluid Intelligence Impairment status whereas the Cognitive Impairment status appeared a predominant tendency for stability. Increasing age played a significant role in fluid intelligence impairment and cognitive impairment process. Female and individuals with nursing home might be at higher risk of subsequent fluid intelligence impairment, while higher education did not protect against fluid intelligence impairment. These findings highlighted the usefulness to adopt a person-centered approach rather than a variable-centered approach, suggesting directions for future research and tailored interventions approaches to older adults with particular characteristics.     

Haploidentical donor transplants for severe aplastic anemia

Haploidentical stem cell transplantation (HAPLO) is being increasingly used, and significant progress has been made both with ex vivo T-cell depleted grafts as well as with unmanipulated marrow or peripheral blood grafts. We here review the current status of HAPLO grafts in patients with acquired severe aplastic anemia. Several transplant platforms have been tested, to overcome graft severe rejection and graft vs host disease (GvHD): these include differences in the conditioning regimen, in graft source and graft manipulation, and in GvHD prophylaxis. The latter include ex vivo T-cell depletion and/or antithymocyte globulin and/or high dose post-transplant cyclophosphamide. Some programs also include the use of marrow or cord blood mesenchymal stem cells, infused at the time of transplantation. Extremely encouraging results are being reported especially in the pediatric population, but also in young adults: we will review reports on 375 patients, with an average rejection rate of 6%, grade II-IV GvHD of 23% and 1-year survival of 80%. Finally we will discuss the place of HAPLO transplants in the context of alternative donor grafts for acquired aplastic anemia.     

Lymphopenic community-acquired pneumonia is associated with a dysregulated immune response and increased severity and mortality

ObjectivesLymphopenic (<724 lymphocytes/µL) community-acquired pneumonia (L-CAP) is an immunophenotype with an increased risk of mortality. We aimed to characterize the l-CAP immunophenotype though lymphocyte subsets and the inflammatory response and its relationship with severity at presentation and outcome.MethodsProspective study of 217 immunocompetent patients hospitalized for CAP. Lymphocyte subsets (CD4⁺, CD8⁺, CD19⁺, and natural killer [NK] cells) and inflammatory cytokines were analyzed on days 1 and 4, and immunoglobulin subclasses were analyzed on day 1 in a nested group.Results39% of patients showed l-CAP, with decreased levels of all lymphocyte subsets with a partial recovery of CD4⁺ and CD8⁺ cells by day 4. l-CAP patients exhibited higher initial severity and systemic levels of interleukin (IL)-8, IL-10, granulocyte colony-stimulating factor, and monocyte chemoattractant protein-1. Initial IgG2 levels were lower in patients with <724 lymphocytes/µL and positively correlated with ALC, CD4⁺, and CD19⁺ cell counts. Low CD4⁺ counts (<129 cells/µL) also independently predicted 30-day mortality after adjusting for age, gender, and the CURB-65 score.Conclusionsl-CAP is characterized by CD4⁺ depletion, a higher inflammatory response, and low IgG2 levels that correlated with greater severity at presentation and worse prognosis. l-CAP is an immunophenotype useful for rapidly recognizing severity.     

Stable long‐term risk of leukaemia in patients with severe congenital neutropenia maintained on G‐CSF therapy

In severe congenital neutropenia (SCN), long‐term therapy with granulocyte colony‐stimulating factor (G‐CSF) has reduced mortality from sepsis, revealing an underlying predisposition to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML). We have reported the early pattern of evolution to MDS/AML, but the long‐term risk remains uncertain. We updated a prospective study of 374 SCN patients on long‐term G‐CSF enrolled in the Severe Chronic Neutropenia International Registry. Long‐term, the annual risk of MDS/AML attained a plateau (2·3%/year after 10 years). This risk now appears similar to, rather than higher than, the risk of AML in Fanconi anaemia and dyskeratosis congenita.     

A Multiethnic Study of Pre-Diabetes and Diabetes in LMIC

BackgroundDiabetes mellitus is one of the leading causes of death and disability worldwide. Approximately three-quarters of people with diabetes live in low- and middle-income countries, and these countries are projected to experience the greatest increase in diabetes burden.ObjectivesWe sought to compare the prevalence, awareness, treatment, and control of diabetes in 3 urban and periurban regions: the Southern Cone of Latin America and Peru, South Asia, and South Africa. In addition, we examined the relationship between diabetes and pre-diabetes with known cardiovascular and metabolic risk factors.MethodsA total of 26,680 participants (mean age, 47.7 ± 14.0 years; 45.9% male) were enrolled in 4 sites (Southern Cone of Latin America = 7,524; Peru = 3,601; South Asia = 11,907; South Africa = 1,099). Detailed demographic, anthropometric, and biochemical data were collected. Diabetes and pre-diabetes were defined as a fasting plasma glucose ≥126 mg/dl and 100 to 125 mg/dl, respectively. Diabetes control was defined as fasting plasma glucose <130 mg/dl.ResultsThe prevalence of diabetes and pre-diabetes was 14.0% (95% confidence interval [CI]: 13.2% to 14.8%) and 17.8% (95% CI: 17.0% to 18.7%) in the Southern Cone of Latin America, 9.8% (95% CI: 8.8% to 10.9%) and 17.1% (95% CI: 15.9% to 18.5%) in Peru, 19.0% (95% CI: 18.4% to 19.8%) and 24.0% (95% CI: 23.2% to 24.7%) in South Asia, and 13.8% (95% CI: 11.9% to 16.0%) and 9.9% (95% CI: 8.3% to 11.8%) in South Africa. The age- and sex-specific prevalence of diabetes and pre-diabetes for all countries increased with age (p < 0.001). In the Southern Cone of Latin America, Peru, and South Africa the prevalence of pre-diabetes rose sharply at 35 to 44 years. In South Asia, the sharpest rise in pre-diabetes prevalence occurred younger at 25 to 34 years. The prevalence of diabetes rose sharply at 45 to 54 years in the Southern Cone of Latin America, Peru, and South Africa, and at 35 to 44 years in South Asia. Diabetes and pre-diabetes prevalence increased with body mass index. South Asians had the highest prevalence of diabetes and pre-diabetes for any body mass index and normal-weight South Asians had a higher prevalence of diabetes and pre-diabetes than overweight and obese individuals from other regions. Across all regions, only 79.8% of persons with diabetes were aware of their diagnosis, of these only 78.2% were receiving treatment, and only 36.6% were able to attain glycemic control.ConclusionsThe prevalence of diabetes and pre-diabetes is alarmingly high among urban and periurban populations in Latin America, South Asia, and South Africa. Even more alarming is the propensity for South Asians to develop diabetes and pre-diabetes at a younger age and lower body mass index compared with individuals from other low and middle income countries. It is concerning that one-fifth of all people with diabetes were unaware of their diagnosis and that only two-thirds of those under treatment were able to attain glycemic control. Health systems and policy makers must make concerted efforts to improve diabetes prevention, detection, and control to prevent long-term consequences.     

Prophylactic managements of hepatitis B viral infection in liver transplantation

Liver transplantation (LT) is a considerably effective treatment for patients with end-stage hepatitis B virus (HBV)-related liver disease. However, HBV infection often recurs after LT without prophylaxis. Since the 1990s, the treatment for preventing HBV reinfection after LT has greatly progressed with the introduction of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NAs), resulting in improved patient survival. The combination therapy consisting of high-dose HBIG and lamivudine is highly efficacious for preventing the recurrence of HBV infection after LT and became the standard prophylaxis for HBV recurrence. However, mainly due to the high cost of HBIG treatment, an alternative protocol for reducing the dose and duration of HBIG has been evaluated. Currently, combination therapy using low-dose HBIG and NAs is considered as the most efficacious and cost-effective prophylaxis for post-LT HBV reinfection. Recently, NA monotherapy and withdrawal of HBIG from combination therapy, along with the development of new, potent high genetic barrier NAs, have provided promising efficacy, especially for low-risk recipients. This review summarizes the prophylactic protocol and their efficacy including prophylaxis of de novo HBV infection from anti-HBc antibody-positive donors. In addition, challenging approaches such as discontinuation of all prophylaxis and active immunity through hepatitis B vaccination are discussed.     

Neoadjuvant therapy for patients with borderline resectable pancreatic cancer: A systematic review and meta-analysis of response and resection percentages

BackgroundWe systematically reviewed and performed a meta-analysis of the available data regarding neoadjuvant chemo- and/or radiotherapy with special emphasis on tumor response/progression rates, toxicities, and clinical benefit, i.e. resection probabilities and survival estimates.Methods and findingsTrials were identified by searching PUBMED, MEDLINE, and the Cochrane Central Register of Controlled Trials from 1966 to Feb 2015. A total of 18 studies (n = 959) were analyzed. the estimated fraction of patients with complete response was 2.8% (CI 0.8–4.7%) and with partial response 28.7% (CI 18.9%–38.5%). Stable disease was averaged to 45.9% (CI 32.9%–58.9%) in all patients and tumor progression under therapy occurred by estimation in 16.9% (CI 10.2%–23.6%) of the patients. The weighted frequency of those who underwent resection was 65.3% (CI 54.2%–76.5%), and the proportion of R0 resection amounted to 57.4% (CI 48.2%–66.5%). The weighted mean of median survival amounted to 17.9 months (range: 14.7–21.2 months) for the overall cohort of patients, 25.9 months (range: 21.1–30.7 months) for those who were resected, and 11.9 months (range: 10.4–13.5 months) for unresected patients.ConclusionsThe resection and R0 resection rates in the group of borderline resectable tumor patients after neoadjuvant therapy are similar to the resectable tumor patients, much higher than those in unresectable tumor patients. The survival estimates of borderline resectable tumor patients after neoadjuvant therapy were similar to resectable tumor patients. Patients with borderline resectable pancreatic cancer should be included in neoadjuvant protocols and subsequently be reevaluated for resection. How to find chemo-responsiveness before neoadjuvant chemotherapy so as to give individualized treatment is still an important issue.